angiotensinogen and Aortic-Coarctation

Even after excellent repair of aortic coarctation without restenosis there are limitations in exercise capacity at long-term follow-up. This study was performed to assess the contribution of inherited genomic polymorphisms to exercise capacity in patients without restenosis.. 122 patients aged 17-72 years, 46 female, 76 male, seen 2-27 years after repair of aortic coarctation with a residual brachial-ankle-gradient ≤20 mmHg were investigated. Genomic polymorphism of angiotensin converting enzyme (ACE I/D), angiotensinogen (AGT, c.704C > T), angiotensin II receptor type 1 (AGTR1, c.1166A > C), endothelin 1 (EDN1, EDN1/ex5-c.5665G > T), G protein (GNB3, c.825C > T), and two polymorphisms each of the ß1-adrenoreceptor (ADRB1, c.145G > A and c.1165C > G), ß2-adrenoreceptor (ADRB2, c.46A > G and c.79C > G), and endothelial NO synthase (NOS3, intron 4 I/D and NOS3, c.894G > T) were determined by PCR amplification and fragment length analysis. Exercise capacity was determined by an upright bicycle exercise test.. Only the c.46A > G polymorphism of the ADRB2 (p = 0.024) and the c.704T > C AGT polymorphism (p = 0.042) were positively correlated with peak workload. Patients with one or especially two polymorphic alleles showed a significant higher exercise performance compared with those patients homozygous for the wild type.. In contrast to a previous study in heart failure patients, after coarctation repair adults had a better exercise capacity with the G allele of the ß2-receptor c.46A > G polymorphism. Therefore, the exercise capacity of coarctation patients does not profit from an enhanced down regulation of their beta receptors.

Topics: Adolescent; Adult; Aged; Angiotensinogen; Aortic Coarctation; Down-Regulation; Exercise Test; Exercise Tolerance; Female; Genetic Predisposition to Disease; Humans; Hypertension; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Prospective Studies; Receptors, Adrenergic, beta-2; Young Adult

Catecholaminergic and angiotensinergic systems are involved in the neural control of blood pressure. The present study analysed the expression of tyrosine hydroxylase (TH), a key enzyme for catecholamine synthesis and of angiotensinogen (AGT), the precursor of angiotensin II (Ang II), in areas of the central nervous system (CNS) involved with cardiovascular regulation such as nucleus tractus solitarius (NTS), ventrolateral medulla (VLM), locus coeruleus (LC) and hypothalamic paraventricular nucleus (PVN) 2 h, 3 and 7 days after aortic coarctated hypertensive rats. In situ hybridization, was employed for the analysis of messenger RNA (mRNA) expression with anatomical resolution. No changes were seen in TH and AGT mRNA expression in the analysed areas 2 h and 3 days after aortic coarctation when compared to the respective sham group. TH mRNA expression was increased in the NTS and LC of rats 7 days after coarctation hypertension when compared to sham rats. Time course analysis, showed an increase in TH mRNA expression in the NTS 7 days after aortic coarctation when compared to 2 h and 3 days groups, as well as an increase in LC 3 days and 7 days following coarctation hypertension in comparison with the 2 h group. Analysis of AGT mRNA in the NTS expression revealed a decrease at 3 days, followed by an increase in mRNA expression 7 days following coarctation hypertension when compared to the sham group. Time course analysis, showed an increase in AGT mRNA expression in the NTS 7 days after coarctation when compared to 2 h and 3 days groups. The results show that TH and AGT mRNA expression changes during the different phases of experimental hypertension, suggesting that the noradrenaline (NOR) and angiotensin II (Ang II) might participate in the modulation/maintenance of coarctation hypertension.

Topics: Angiotensin II; Angiotensinogen; Animals; Aortic Coarctation; Blood Pressure; Brain; Brain Stem; Catecholamines; Disease Models, Animal; Gene Expression; Hypertension; Male; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred WKY; RNA, Messenger; Time Factors; Tyrosine 3-Monooxygenase; Up-Regulation

Topics: Angiotensinogen; Animals; Aorta, Thoracic; Aortic Coarctation; Blood Pressure; Disease Models, Animal; Gene Expression; Hypertension, Renal; Kidney; Male; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Angiotensin; Renin; Renin-Angiotensin System; RNA, Messenger; Tissue Distribution